A breeding program has been carried out starting with two miniature pigs from different sources and selecting offspring according to tissue typing procedures aimed at defining the major histocompatibility complex of this species. By this procedure three herds of miniature swine, each homozygous for a different set of histocompatibility antigens at the MHC have been developed. Current projects include: 1) Assessment of survival of organs and tissue transplants among and between members of these herds as a model for tissue typing and transplantation; 2) Purification and characterization of the major histocompatibility antigens of this species, and isolation and characterization of peptides from these antigens for sequence analyses and for assessment of immunologic reactivity; 3) Assessment of the immunologic parameters involved in tolerance to allografts in this species; 4) Detection and characterization of intra-MHC recombinants. Two intra-MHC recombinants have been obtained and bred to homozygosity. Kidney transplants utilizing these new recombinants have shown that selective matching for Class II antigens frequently permits long-term kidney graft survival across a Class I difference. The mechanism of this apparent tolerance is under further study; and 5) Bone marrow transplants in miniature swine. The effect of mixing autologous plus allogeneic marrow in the reconstituting inoculum are being examined. This modality is being assessed as a specific preparative regimen for allogeneic organ transplantation.